The development of a stochastic physiologically-based pharmacokinetic model for lead

This presentation describes the development of a prototype Monte Carlo modu le for the physiologically-based pharmacokinetic (PBPK) model for lead, cre ated by Dr Ellen O'Flaherty. The module uses distributions for the followin g: exposure parameters (soil and dust concentrations, daily soil and ingest ion rate, water lead concentration, water ingestion rate, air lead concentr ation, inhalation rate and dietary lead intake); absoption parameters; and key pharmacokinetic parameters (red blood binding capacity and half saturat ion concentration). Distributions can be specified as time-invariant or can change with age. Monte Carlo model predicted blood levels were calibrated to empirically measured blood lead levels for children living in Midvale, U tah (a milling/smelting community). The calibrated model was then evaluated using blood lead data from Palmerton, Pennsylvania (a town with a former s melter) and Sandy, Utah, (a town with a former smelter and slag piles). Our initial evaluation using distributions for exposure parameters showed that the model accurately predicted geometric (GM) blood lead levels of Palmert on and Sandy and slightly over predicted the GSD. Consideration of uncertai nty in red blood cell parameters substantially inflated the GM. Future mode l development needs to address the correlation among parameters and the use of parameters for long-term exposure derived from short-term studies. (C) 2001 Elsevier Science B.V. All rights reserved.